University of Texas Southwestern Medical Center Dallas, TX
Michael Rowley, MD, Hendrikus Vanderveldt, MD, MBA; University of Texas Southwestern Medical Center, Dallas, TX
Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are one of the recognized precursors of pancreatic ductal adenocarcinoma (PDAC). Detection of precancerous and early stage neoplastic lesions is critical given the poor 5-year survival rates of PDAC. Although malignant transformation occurs in the minority of lesions, those that do transform are more likely to have high-risk genomic mutations. Next generation sequencing (NGS) identifies IPMNs with these high-risk mutations. African Americans have a higher incidence of PDAC than Caucasians. Multiple factors have been identified that partly explain this difference. However, genomic variability in IMPNs between races has not been studied.
Aim: Evaluate differences in high-risk genomic mutations in IPMNs between African Americans and Caucasians. Methods: Single institution retrospective cohort study identifying 94 consecutive patients in 2019 who underwent 100 EUS with FNA or ERCP with fluid sampling of pancreatic cysts or pancreatic duct dilation. Indication for diagnostic sampling was based on standard high-risk criteria by ACG guidelines. All cyst fluid was sent for NGS with PancreaSeq®. Presence of GNAS and/or KRAS mutation confirmed diagnosis of IPMN. High-risk genomic mutations were TP53, PIK3CA, AKT1, PTEN and SMAD4. Clinical demographics and cyst variables were collected: age, gender, race, BMI, history of pancreatitis, diabetes, smoking, family history of PDCA, cyst size, nodules, duct dilation, CEA level and genomic profile. Differences between African Americans and Caucasians compared with univariate analysis; p < 0.05 significant. Logistic regression for presence of high-risk mutations performed; p < 0.05 significant. Results: 53 samples were positive for a GNAS and/or KRAS mutation in 49 patients. Seven of 53 samples (12%) had a high-risk mutation. On univariate analysis, clinical and cyst variables did not differ by race. The rate of high-risk mutations did not differ: 29% in African Americans vs 11% in Caucasians (p = 0.197). However, there was a trend toward increased rate of high-risk mutations in African Americans on logistic regression when controlling for other collected variables (p = 0.071). No other variables were independently predictive of high-risk mutations. Discussion: Higher rates of high-risk genomic mutations in IPMNs might be a factor in explaining the higher rates of PDAC in African Americans. Larger studies are needed to evaluate these findings.
Disclosures: Michael Rowley indicated no relevant financial relationships. Hendrikus Vanderveldt indicated no relevant financial relationships.